This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 1 diabetes T1D1 is associated with tremendous morbidity and premature mortality. Patients require multiple daily insulin injections throughout their lives as well as close monitoring of their diet and blood sugar levels to prevent disease associated complications. Whole pancreas or islet cell transplantation is available only to a very limited number of patients and necessitates potential lifelong immunosuppressive therapy. Granulocyte colony stimulating factor G-CSF has recently been shown to prevent T1D in the Non Obese Diabetic NOD mouse model of the disease. Those studies demonstrated that the benefits of G-CSF therapy are likely due to mobilization of T regulatory cells Treg from the bone marrow. G-CSF may have the potential to dampen the autoimmune response by acting as a potent immunomodulator involving Treg stimulation. In this study we will use the long acting pegylated GCSF Neulasta. Subjects will be randomly assigned to receive either Neulasta or placebo. We will treat 21 individuals with T1D having persistent stimulated c-peptide 0.2 pmol/ml. Fourteen patients will be given a 12 week course of Neulasta 10 mcg/kg/d every 2 weeks and 7 patients will be given the placebo with equal volumes of normal saline provided in identically marked vials. Our primary goals will be to document the safety of pegylated G-CSF therapy in the T1D population and to document the augmentation in the Treg response with therapy. As secondary goals, we aim to study changes in metabolic function associated with pegylated G-CSF therapy.